Comination effect of reserpine with antitumor agents in L1210

The antileukemic combined effect of reserpine with 1-gamma-chloropropyl-2-chloromethylpiperidine hydrobromide (CAP-2) and other antitumor agents was studied on mouse leukemia L1210 in comparison with the effects of other Rauwolfia alkaloids and sympatholytic drugs. When reserpine was administered by a single ip injection (2.5 mg/kg) on day 1, the effect of subsequent administration of CAP-2, mitomycin-C, or vinblastine was synergistically enhanced. In this combination with reserpine, the acute lethality of CAP-2 on the host animals was apparently decreased. Among other sympatholytic drugs, rescinnamine, a central nervous system depressant, slightly potentiated the antitumor effect of CAP-2. On the other hand, when reserpine-induced hypothermia was prevented by maintenance of the ambient temperature at 30 degrees, the synergistic combined effect of reserpine was diminished. Chlorpromazine-induced hypothermia did not influence the antitumor effect of CAP-2. It may be concluded that the antileukemic synergism depends partially on the interaction between reserpine and CAP-2 or other antitumor agents in relation to body temperature and/or action on the central nervous system in leukemic mice.